Sex and Gender Differences in Testing, Hospital Admission, Clinical Presentation, and Drivers of Severe Outcomes From COVID-19.

BACKGROUND: Males experience increased severity of illness and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with females, but the mechanisms of male susceptibility are unclear. METHODS: We performed a retrospective cohort analysis of SARS-CoV-2 testing and admission data at 5 hospitals in the Maryland/Washington DC area. Using age-stratified logistic regression models, we quantified the impact of male sex on the risk of the composite outcome of severe disease or death (World Health Organization score 5-8) and tested the impact of demographics, comorbidities, health behaviors, and laboratory inflammatory markers on the sex effect. RESULTS: Among 213 175 SARS-CoV-2 tests, despite similar positivity rates, males in age strata between 18 and 74 years were more frequently hospitalized. For the 2626 hospitalized individuals, clinical inflammatory markers (interleukin-6, C-reactive protein, ferritin, absolute lymphocyte count, and neutrophil:lymphocyte ratio) were more favorable for females than males (P < .001). Among 18-49-year-olds, male sex carried a higher risk of severe outcomes, both early (odds ratio [OR], 3.01; 95% CI, 1.75 to 5.18) and at peak illness during hospitalization (OR, 2.58; 95% CI, 1.78 to 3.74). Despite multiple differences in demographics, presentation features, comorbidities, and health behaviors, these variables did not change the association of male sex with severe disease. Only clinical inflammatory marker values modified the sex effect, reducing the OR for severe outcomes in males aged 18-49 years to 1.81 (95% CI, 1.00 to 3.26) early and 1.39 (95% CI, 0.93 to 2.08) at peak illness. CONCLUSIONS: Higher inflammatory laboratory test values were associated with increased risk of severe coronavirus disease 2019 for males. A sex-specific inflammatory response to SARS-CoV-2 infection may underlie the sex differences in outcomes.

Sex and gender differences in COVID testing, hospital admission, presentation, and drivers of severe outcomes in the DC/Maryland region.

BACKGROUND: Rates of severe illness and mortality from SARS-CoV-2 are greater for males, but the mechanisms for this difference are unclear. Understanding the differences in outcomes between males and females across the age spectrum will guide both public health and biomedical interventions. METHODS: Retrospective cohort analysis of SARS-CoV-2 testing and admission data in a health system. Patient-level data were assessed with descriptive statistics and logistic regression modeling was used to identify features associated with increased male risk of severe outcomes. RESULTS: In 213,175 SARS-CoV-2 tests, despite similar positivity rates (8.2%F vs 8.9%M), males were more frequently hospitalized (28%F vs 33%M). Of 2,626 hospitalized individuals, females had less severe presenting respiratory parameters and males had more fever. Comorbidity burden was similar, but with differences in specific conditions. Medications relevant for SARS-CoV-2 were used at similar frequency except tocilizumab (M>F). Males had higher inflammatory lab values. In a logistic regression model, male sex was associated with a higher risk of severe outcomes at 24 hours (odds ratio (OR) 3.01, 95%CI 1.75, 5.18) and at peak status (OR 2.58, 95%CI 1.78,3.74) among 18-49 year-olds. Block-wise addition of potential explanatory variables demonstrated that only the inflammatory labs substantially modified the OR associated with male sex across all ages. CONCLUSION: Higher levels of clinical inflammatory labs are the only features that are associated with the heightened risk of severe outcomes and death for males in COVID-19. TRIAL REGISTRATION: NA. FUNDING: Hopkins inHealth; COVID-19 Administrative Supplement (HHS Region 3 Treatment Center), Office of the ASPR; NIH/NCI U54CA260492 (SK), NIH/NIA U54AG062333 (SK).

Machine learning for identification of surgeries with high risks of cancellation.

Surgery cancellations waste scarce operative resources and hinder patients' access to operative services. In this study, the Wilcoxon and chi-square tests were used for predictor selection, and three machine learning models - random forest, support vector machine, and XGBoost - were used for the identification of surgeries with high risks of cancellation. The optimal performances of the identification models were as follows: sensitivity - 0.615; specificity - 0.957; positive predictive value - 0.454; negative predictive value - 0.904; accuracy - 0.647; and area under the receiver operating characteristic curve - 0.682. Of the three models, the random forest model achieved the best performance. Thus, the effective identification of surgeries with high risks of cancellation is feasible with stable performance. Models and sampling methods significantly affect the performance of identification. This study is a new application of machine learning for the identification of surgeries with high risks of cancellation and facilitation of surgery resource management.

Vascular Access Type Was Not Associated with Mortality and the Predictors for Cardiovascular Death in Elderly Chinese Patients on Hemodialysis.

OBJECTIVES: Current studies suggest arteriovenous fistula (AVF) and arteriovenous graft as superior vascular access (VA) types for elderly hemodialysis (HD) patients due to better outcomes. This study aimed to examine the impact of VA type on cardiovascular and all-cause mortality as well as the predictors for outcome in elderly Chinese patients. METHODS: Patients who initiated HD aged ≥70 years and received a primary VA creation at the West China Hospital were enrolled in this retrospective study. Clinical characteristics, maturation, utilization, conversion of VA, and outcomes were collected. The observational period for each patient was from the point of the first permanent VA creation to the last time of follow-up. Kaplan-Meier and multivariate regression analysis were employed. RESULTS: A total of 358 elderly Chinese HD patients with a median age of 74 (72-78) years were analyzed. During the study period of 25.8 (12-43) months, 54 (15.1%) and 113 patients (15.1%) died of cardiovascular events and all-cause, respectively. With regard to VA type, the modality of AVF, tunneled cuffed central venous catheter (tcCVC), or AVF and tcCVC was not associated with mortality. Furthermore, diastolic blood pressure (DBP) and congestive heart failure (CHF) were the independent predictors for cardiovascular mortality. CONCLUSIONS: The modality of VA types showed an insignificant effect on mortality in elderly Chinese population, while preoperative DBP and the presence of CHF might be used for the risk assessment of cardiovascular death. Disparities among nations in the areas of VA and HD necessitate additional studies.

Microbial and metabolomic remodeling by a formula of Sichuan dark tea improves hyperlipidemia in apoE-deficient mice.

Medicine-food homology is a long-standing concept in traditional Chinese medicine. YiNianKangBao (YNKB) tea is a medicine-food formulation based on Sichuan dark tea (Ya'an Tibetan tea), which is traditionally used for its lipid-lowering properties. In this study, we evaluated the effects of YNKB on dyslipidemia and investigated the mechanism underlying its correlation with gut microbiota and serum metabolite regulation. Wild-type mice were fed a normal diet as a control. Male ApoE-/- mice were randomly divided into three high-fat diet (HFD) groups, a model group, and two treated groups (100, 400 mg/kg/d for low, high-dose), and fed by gavage for 12 weeks. Serum lipid levels, composition of gut microbiota, and serum metabolites were then analyzed before treatment with YNKB. We extracted the ingredients of YNKB in boiled water for one hour. YNKB supplementation at a high dose of 400 mg/kg/day reduced bodyweight gains (relative epididymal fat pad and liver weight), and markedly attenuated serum lipid profiles and atherosclerosis index, with no significant differences present between the low-dose treatment and HFD groups. Gut microbiota and serum metabolic analysis indicated that significant differences were observed between normal, HFD, and YNKB treatment groups. These differences in gut microbiota exhibited strong correlations with dyslipidemia-related indexes and serum metabolite levels. Oral administration of high-dose YNKB also showed significant lipid-lowering activity against hyperlipidemia in apoE-deficient mice, which might be associated with composition alterations of the gut microbiota and changes in serum metabolite abundances. These findings highlight that YNKB as a medicine-food formulation derived from Sichuan dark tea could prevent dyslipidemia and improve the understanding of its mechanisms and the pharmacological rationale for preventive use.

Androgen-dependent loss of muscle BDNF mRNA in two mouse models of SBMA.

Transgenic expression of neurotrophic factors in skeletal muscle has been found to protect mice from neuromuscular disease, including spinal bulbar muscular atrophy (SBMA), triggering renewed interest in neurotrophic factors as therapeutic agents for treating neuromuscular disease. Because SBMA is an androgen-dependent disease, and brain-derived neurotrophic factor (BDNF) mediates effects of androgens on neuromuscular systems, we asked whether BDNF expression is impaired in two different transgenic (Tg) mouse models of SBMA, the so called "97Q" and "myogenic" SBMA models. The 97Q model globally overexpresses a full length human AR with 97 glutamine repeats whereas the myogenic model of SBMA overexpresses a wild-type rat androgen receptor (AR) only in skeletal muscle fibers. Using quantitative PCR, we find that muscle BDNF mRNA declines in an androgen-dependent manner in both models, paralleling changes in motor function, with robust deficits (6-8 fold) in both fast and slow twitch muscles of impaired Tg males. Castration rescues or reverses disease-related deficits in muscle BDNF mRNA in both models, paralleling its effect on motor function. Moreover, when disease is acutely induced in Tg females, both motor function and muscle BDNF mRNA expression plummet, with the deficit in muscle BDNF emerging before overt motor dysfunction. That androgen-dependent motor dysfunction is tightly associated with a robust and early down-regulation of muscle BDNF mRNA suggests that BDNF delivered to skeletal muscle may have therapeutic value for SBMA.